Nivolumab, Pembrolizumab Compete for Top Choice in NSCLC Treatment

Having two PD-1 agents available for patients with non–small cell lung cancer (NSCLC) across all histologies has proven to be an “embarrassment of riches” in the treatment paradigm, according to Benjamin Levy, MD.

Pembrolizumab (Keytruda) was granted an accelerated approval by the FDA as a treatment for patients with pretreated advanced NSCLC across all histologies whose tumors express PD-L1 in October 2015. Pembrolizumab was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progressed on or after platinum-containing chemotherapy or EGFR- or ALK-targeted agents in patients harboring those mutations.

Most recently, the FDA accepted a supplemental new drug application for pembrolizumab as a treatment for patients with advanced NSCLC with PD-L1 expression on >1% of tumor cells.

Also in October 2015, the FDA expanded the approval of nivolumab (Opdivo) to include patients with nonsquamous NSCLC who progress on or following platinum-based chemotherapy, or EGFR- or ALK-targeted agents in patients who have those mutations.

In an interview with OncLive, Levy, assistant professor of Medicine, Hematology, and Medical Oncology at Mount Sinai Hospital, discusses how nivolumab and pembrolizumab have impacted the treatment landscape of NSCLC, how to choose between the two for patients, and what biomarkers are in development for PD-1/PD-L1 agents.

OncLive: How have the approvals of nivolumab and pembrolizumab in the second-line setting changed the treatment paradigm of NSCLC?

Levy: Nivolumab and pembrolizumab have completely created a completely new therapy paradigm for patients with both squamous and nonsquamous cell NSCLC.

Nivolumab was compared with docetaxel as a second-line drug in both the squamous and nonsquamous population in 2 competing CheckMate studies. In both of those studies, nivolumab provided a meaningful improvement in overall survival. Because of that improvement, nivolumab is now approved as a second-line drug for patients who are platinum-refractory.

We need to remember that, most often, lung cancer trials fail to show survival advantages. If you look at the data, probably 90% to 95% of all phase III lung cancer trials fail to show this. There are 2 that we have, and they have been published in The New England Journal of Medicine. It has completely changed how we treat patients in the second-line setting.

Pembrolizumab is the other checkpoint inhibitor that was recently approved from the KEYNOTE-010 study. It showed very competitive response rates—close to 40% to 45% in patients with PD-L1–expressing lung cancers that were squamous or adenocarcinoma. The difference between nivolumab and pembrolizumab is that pembrolizumab requires patients to be PD-L1–positive, and nivolumab does not have that in its approval.

Overall, these drugs are great. It’s an embarrassment of riches for patients. They are checkpoint inhibitors, have very similar activity, and very similar adverse events. It just so happens that pembrolizumab does require PD-L1 testing and nivolumab does not.

How else would you choose between the two agents when deciding on treatment for a patient?

It really comes down to whether your institution is doing PD-L1 testing, or whether the testing can be done at a third-party laboratory. At our institution, we have a lot of problems with having enough tissue available. This is not only for molecular interrogation, but also for samples to be provided for clinical trials. I have not been routinely testing for PD-L1 in my patient population because I can give nivolumab regardless of PD-L1 status.

What are your thoughts on the value of PD-L1 as a biomarker?

What we know is it may not be the best biomarker that predicts efficacy to these drugs. I have had many patients that had been screened for trials, who have been PD-L1–negative, end up getting nivolumab, and they do great. For me, I have been more commonly using nivolumab.

That being said, I think pembrolizumab is a great drug. It works just as well in patients as nivolumab. I have been using pembrolizumab in a clinical trial that I am leading, and I have seen wonderful things. It’s very similar to what I see with nivolumab. However, in routine use outside of a clinical trial, I’m more often using nivolumab. This is just based on that PD-L1 testing that has to be done.

What is the status of the development of other biomarkers for PD-1/PD-L1 agents?

Right now, the search is on to find the optimal biomarker that predicts efficacy to these drugs. We started out with PD-L1 in the tissue. However, the problem with the immunohistochemistry test is that there are different platforms that test for PD-L1; there are different cutoff values.